The broad research objectives of this project are to investigate factors which control or modify insulin secretion by the isolated perfused rat or hamster pancreas. The use of such an in vitro preparation makes it possible to study the intrinsic properties of the beta cell in a well-controlled environment which mimics as closely as possible the normal physiological state of the tissue. Therefore, this study will be devoted to investigation of the direct mechanism(s) controlling or modulating the insulin secretory phenomenon. Any information thus gathered concerning the normal insulin secretory process will then hopefully aid in understanding the deficient mechanism(s) which exists in the disease diabetes mellitus. Such knowledge should then lead to the development of a means of treating the pathological conditions which give rise to the diabetic state. In addition to the above, a major objective of this project is the understanding of the secretory mechanism in general and its subsequent applications to normal and pathological conditions involving other secretory systems.